Interferon (IFN) and double-stranded RNA (dsRNA) are interdependent in exerting many of their biological actions. In recognition of this fact, IFN and dsRNA are considered as a comprehensive, total system in characterizing the action, induction, and regulation of this system in both human and Syrian hamster cells. This study encompasses five major projects. (1)\Understanding the structure-function relationship of dsRNA in the induction of IFN synthesis and in its action as a cofactor in mediating the biological actions of the IFN system. The strategy involved in this project is systematic chemical modification of dsRNA and the use of anti-IFN antibody to dissect out the relative contributions of IFN and dsRNA to the total biological effect. (2)\Characterizing the anticellular effects of IFN and dsRNA both in inhibiting the proliferation of normal and neoplastic cells as well as in suppressing progression in neoplastic transformation and the neoplastic phenotype. (3)\Characterizing the changes in gene expression accompanying the antiviral and anticellular state in human tumor cells. The effects of both dsRNA and IFN on changes in gene expression will be extrapolated to previously determined cellular phenotypes in sensitive and resistant cells in an effort to determine the molecular basis of sensitivity and resistance to dsRNA and IFN. (4)\Characterizing the expression of the IFN system during embryogenesis of the Syrian hamster and determining its influence on the developmental process. Study of this differentiation system will provide insight into the relationship between expressions of the various biological and biochemical components of IFN as it is being developed from a dormant stage to an operational stage. (5)\Understanding the basic mechanisms involved in regulating IFN synthesis. Emphasis is placed on identifying those factors responsible for shut off of IFN synthesis. This study may result in the development of methods to circumvent the shut off of IFN synthesis, which would greatly enhance IFN production for practical use. Knowledge obtained from these combined mechanistic studies is vital for developing a rationale for the application of IFN and dsRNA as antiviral and anticancer drugs. (A)